1. Studies of the role of the viral envelope gene in mediating brain disease after infection by polytropic virus FMCF 98D have identified two separate regions of the env sequence as virulence determinants. Recent work has identified the precise amino acids in one region of the viral envelope involved in this effect. Interestingly there was no correlation between viral load and induction of disease, suggesting that differences in levels of viral replication did not account for the differences in disease induction. 2. Current results suggest that CD4-positive T cells are required for the Rfv-3 effect on induction of IgG or IgM virus neutralizing antibodies in all mouse strains tested so far. Further efforts are also in progress to more accurately determine the chromosomal location of this gene as a prelude to attempting direct cloning experiments.